The central nervous system is known to play an important role in body weight regulation through its control of behavioral, hormonal, and metabolic events. However, major questions about the role of the central nervous system in obesity remain unanswered. These questions include: the identity of the specific neural populations that comprise the regulatory systems and the nature of the effector mechanisms by which events in the central nervous system affect adipose tissue. The proposed experiments use behavioral, biochemical and anatomical techniques to test current hypotheses about the answers to these questions. Neurochemically-defined systems in the brain are the focus of recent attempts to specify the anatomical substrate for body weight regulation. The proposed research examines the involvement of catecholamine-containing neurons in disorders of weight regulation. In genetically obese mice in which abnormalities have been uncovered in catacholaminergic system, the relationship of spontaneously occurring obesity to monoamine function will be studied. In the diabetes mouse, reduction of central norepinephrine levels improves the obesity syndrome. Experiments will be undertaken to explain this phenomenon. Thus, the question of the effector mechanisms in the central control of body weight regulation will be investigated. In the most widely studied models of abnormal weight regulation, rats with either ventromedial or lateral hypothalamic lesions, altered autonomic function is apparent. Data is accumulating to suggest that a change in the sympathetic nervous system may be important in weight changes that follow the lesions. Experiments are proposed to examine the contribution of central catecholamines to disturbances in autonomic function related to feeding and body weight.